Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone
Authors: Edward Man-Lik Choi, Boris Lacarra, Muhammed O Afolabi, Boni Maxime Ale, Frank Baiden, Christine Bétard, Julie Foster, Benjamin Hamzé, Christine Schwimmer, Daniela Manno, Eric D’Ortenzio, David Ishola, Cheick Mohamed Keita, Babajide Keshinro, Yusupha Njie, Wim van Dijck, Auguste Gaddah, Dickson Anumendem, Brett Lowe, Renaud Vatrinet, Bolarinde Joseph Lawal, Godfrey T Otieno, Mohamed Samai, Gibrilla Fadlu Deen, Ibrahim Bob Swaray, Abu Bakarr Kamara, Michael Morlai Kamara, Mame Aminata Diagne, Dickens Kowuor, Chelsea McLean, Bailah Leigh, Abdoul Habib Beavogui, Maarten Leyssen, Kerstin Luhn, Cynthia Robinson, Macaya Douoguih, Brian Greenwood, Rodolphe Thiébaut, Deborah Watson-Jones, T Mooney, L Conteh, MS Bangura, MA Bangura, H Jalloh, I Kamara, M Kamara, S Koroma, M Sesay, MT Sesay, AT Deen, A Kamara, EL Kamara, SLM Kamara, AH Koroma, IS Mansaray, MJ Massaquoi, A Nabie, D Kowuor, Y Njie, L Odeny, M Sheku, AB Jalloh, A Sow, E Swaray, F Mansaray, T Sessie, J-HC Sunders, SI-S Turay, J Weekes, M Pessima, A Wurie, M Conteh, MI Jalloh, PBD Kamara, DP Kanneh, M Kanneh, I Komeh, M Koroma, M Kuyateh, FF Mansaray, B Leigh, D Watson-Jones, M Samai, GF Deen, T Sesay, P Piot, B Greenwood, S Lees, H Larson, M Afolabi, D Ishola, F Baiden, F Faye, D Tindanbil, MM Kamara, IB Swaray, A Bangura, AB Kamara, FE Morovia, JA Kallon, M Murray, F Sesay, F Suma, IG Sesay, EM Choi, D Manno, J Foster, R Rwezaula, I Akhigbe, H Adetola, B Kamara, B Lowe, B Lawal, B Kohn, GO Tuda, F Koroma, A Kamara, G Bangura, MT Kroma, L Fofanah, A Pessima, M Rogers, O Sheriff, J Fangawa, S Foday, I Jabbie, HA Mansaray, K Sesay, HB Jakema, MF Sheku, KFN Jalloh, M Kabba, F Kanjie, AP Kanu, G Kassa-Koroma, M Jusu, B Koroma, P Borboh, A Kallon, K van Roey, P Conteh, M Samura, V Gandie, M Marrah, J Kalokoh, MI Bangura, N Connor, S Saidu, AS Turay, A Lahai, CL Johnson, DB Kogba, W Vincent, M Bangura, A Tengbeh, K Bangura, R Kabia, AM Nyakoi, S Lee, D Nyaberi, S Ndingi, L Nyallay, AR Bangura, B Idriss, M Sillah, W Mackay, T Murray, J Edem-Hotah, T Fatorma, M Kamara, S Bangura, E Bonnie, M Sannoh, S Malcolm, J Brown, E Snowden, K Howard, A Ojugo, C Massin-Shepherd, AH BEAVOGUI, CM KEITA, OK CAMARA, JPY GUILAVOGUI, H BAH, MA SAMOURA, D MUAMBA, B SEMAKUBA, AK CAMARA, AS KABA, M BERERD-CAMARA, M YARADOUNO, M DECHENAUD, MT CAMARA, J TAMBALOU, M HABA, SD DIALLO, A THEA, N DOUMBOUYA, ML FOFANA, M BEAVOGUI, AA CAMARA, JT BEAVOGUI, W DIOUF, A AUGIER, E BARTE DE SAINTE FARE, B SIVAHERA MUYISA, S SANI, R VATRINET, B HAMZE, B LACARRA, E D’ORTENZIO, B ALE, C BETARD, L RICHERT, D OULAI, M KANTE, A-A SOUTTHIPHONG, C SCHWIMMER, R THIÉBAUT, A OTTAVI, S COUFFIN-CADIERGUES, H ESPEROU, SP Chai, W Buth, K Offergeld, A Menten, N Hammoud, S De Ridder, R Sellecchia, R in ’t Veld, N Fogap, D Anumendem, H Stapleton, T Reijns, J Haydon, L Roza, B Sawyer, S Hoda, J Yee, T De Cnodder, E Hubin, L Telen, J Desai, M Bennet, M Pawlowski, N van Gils, N Boeykens, A Kwasniak, M Ligthart, G Van Roey, E Fernandez, A Gaddah, W van Dijck, S Jingshuang, S Randrasana, C Artis, A Akinbinu, A Poretti, S Van Ballaert, M Harris, M Van Looveren, P Brandt, C Robinson, V Bockstal, C McLean, I Versteege, C Ferrault, A Kaminski, H Vergauwen, CI Kerama, M Bennet, CA Forcheh, N Fogap, CV DiMondi, L Stewart, J Meurer, A Beounitis, J Peeters, C Su, B Keshinro, C Delport, E Sharkie, J Zhang, C Du, K Hu, A Strydom, I Bezem-Aviv, A Wachnicka, P Kumar, S Cheng, K Kang
Journal: The Lancet Global Health (2023)

BackgroundThis study assessed the safety and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo Ebola virus (EBOV) vaccine regimen in infants aged 4–11 months in Guinea and Sierra Leone.MethodsIn this phase 2, randomised, double-blind, active-controlled trial, we randomly assigned healthy infants (1:1 in a sentinel cohort, 5:2 for the remaining infants via an interactive web response system) to receive Ad26.ZEBOV followed by MVA-BN-Filo (Ebola vaccine group) or two doses of meningococcal quadrivalent conjugate vaccine (control group) administered 56 days apart. Infants were recruited at two sites in west Africa: Conakry, Guinea, and Kambia, Sierra Leone. All infants received the meningococcal vaccine 8 months after being randomly assigned. The primary objective was safety. The secondary objective was immunogenicity, measured as EBOV glycoprotein-binding antibody concentration 21 days post-dose 2, using the Filovirus Animal Non-Clinical Group ELISA. This study is registered with ClinicalTrials.gov (NCT03929757) and the Pan African Clinical Trials Registry (PACTR201905827924069).FindingsFrom Aug 20 to Nov 29, 2019, 142 infants were screened and 108 were randomly assigned (Ebola vaccine n=75; control n=33). The most common solicited local adverse event was injection-site pain (Ebola vaccine 15 [20%] of 75; control four [12%] of 33). The most common solicited systemic adverse events with the Ebola vaccine were irritability (26 [35%] of 75), decreased appetite (18 [24%] of 75), pyrexia (16 [21%] of 75), and decreased activity (15 [20%] of 75). In the control group, ten (30%) of 33 had irritability, seven (21%) of 33 had decreased appetite, three (9%) of 33 had pyrexia, and five (15%) of 33 had decreased activity. The frequency of unsolicited adverse events was 83% (62 of 75 infants) in the Ebola vaccine group and 85% (28 of 33 infants) in the control group. No serious adverse events were vaccine-related. In the Ebola vaccine group, EBOV glycoprotein-binding antibody geometric mean concentrations (GMCs) at 21 days post-dose 2 were 27 700 ELISA units (EU)/mL (95% CI 20 477–37 470) in infants aged 4–8 months and 20 481 EU/mL (15 325–27 372) in infants aged 9–11 months. The responder rate was 100% (74 of 74 responded). In the control group, GMCs for both age groups were less than the lower limit of quantification and the responder rate was 3% (one of 33 responded).InterpretationAd26.ZEBOV and MVA-BN-Filo was well tolerated and induced strong humoral responses in infants younger than 1 year. There were no safety concerns related to vaccination.FundingJanssen Vaccines & Prevention and Innovative Medicines Initiative 2 Joint Undertaking.TranslationFor the French translation of the abstract see Supplementary Materials section.